When a drug is administered intravenously or orally, the initial level of drug in the blood rapidly rises to a maximum. This initial level of drug is generally much higher than the therapeutically effective level. For example, FIG. 1 shows that sometimes initial levels of drugs administered orally may reach toxic concentrations resulting in undesirable side-effects. This is known as "overdosing." After the drug is administered and rises to a maximum level in the blood, the level then falls slowly as the drug is distributed, metabolized, excreted, or degraded. Eventually, the level of drug in the blood falls below the therapeutically effective level (i.e., there is "underdosing"). At this point, the drug needs to be re-administered to achieve effectiveness. Maintaining the concentration of drug in the blood between the minimum therapeutically effective level and toxic levels is important. One way to achieve this is to administer lower drug doses to the patient more frequently. This, however, is an unacceptable alternative in most instances.
Transdermal delivery of drugs offers a means of circumventing the problems of overdosing and underdosing that are associated with conventional drug delivery methods. The transdermal delivery of drugs can be designed so that the rate of delivery of the drug closely follows the rate of the clearance of the drug from the environment, thus keeping constant levels of drug in the blood, and reducing drug waste and overdosing problems. FIG. 1 displays the blood levels from transdermal and conventional oral delivery of drugs over a period of time.
In addition to the advantage of being able to control drug delivery rates, transdermal drug delivery also provides a comfortable, convenient and noninvasive way of administering drugs. Gastrointestinal irritation and other side-effects, often associated with oral drug delivery, are eliminated.
However, the amount of drug that can be delivered to a patient transdermally has limitations. Many drugs are poor candidates for transdermal delivery due to limitations on the permeability of the drug through the skin, or the large dose of the drug required for therapeutic efficacy. A partial solution to the dose problem associated with transdermal delivery can be employed when the drug to be delivered is a racemic mixture and most or all of the biological activity of the drug is associated with one enantiomer of the drug.
Delivery of eutomers rather than racemic mixtures to reduce the dose of drug to be delivered is known. For example, the drug Naproxen is manufactured as the racemic mixture and then resolved and sold to patients as the eutomer to reduce the size of the tablets to be used from 1000 mg tablets for the racemic drug to a more practical 500 mg tablets for the eutomer. The maximum reduction in dose that can be achieved when the eutomer is used is 50% since the racemic mixture consists of a 50:50 mixture of the two enantiomers.
Accordingly, it is an object of this invention to provide a pharmaceutical composition for the transdermal delivery of the eutomer of a chiral drug where the clearance value of the eutomer is greater than that of the racemic mixture.
It is another object of this invention to provide a transdermal patch for the delivery of S(-) ketorolac.
These and other objects and features of the invention will be apparent to those skilled in the art from the following detailed description and appended claims when taken in conjunction with the figures.